Photodynamic Therapy During In Vivo Lung Perfusion for Treatment of Lung Metastases
Bibliographic record
Abstract
Isolated lung metastases in sarcoma and colorectal cancer patients are inadequately treated with current standard therapies. In Vivo Lung Perfusion, a novel platform, could overcome limitations to photodynamic therapy treatment volumes by using low cellular perfusate, removing blood, and thus theoretically allowing greater light penetration. Development of personalized photodynamic therapy protocols requires in silico light propagation simulations based on optical properties and maximal permissible photodynamic threshold doses of lung tissue. This approach aims to maximize the effective treatment dose to the lung while avoiding toxicity to healthy lung tissue. Based on this rationale, the overall objective of this thesis is to create a whole-lung perfusion assisted PDT protocol for the treatment of lung metastases demonstrating adequate safety and feasibility to guide clinical translation. To achieve this goal, the first aim is to quantify key biophysical properties necessary for PDT; specifically, the optical properties for blood and low-cellular perfusion and the photodynamic threshold dose for 5-ALA and Chlorin e6. This will demonstrate the difference in light penetration for low cellular perfusate vs. blood. The second aim of this work is to develop a 72-hr porcine In Vivo Lung Perfusion survival model to allow assessment of acute and delayed lung toxicity. This model is validated using an accelerated titration dose-escalation study of delivery of oxaliplatin chemotherapy. The final aim of this work involves combining the previous aims to develop a full treatment protocol. Firstly, a light delivery system is created that can homogenously deliver light to the entire lung, and using Monte Carlo simulation software, can be used to simulate personalized treatment plans. The safety and feasibility of a full treatment protocol of whole-lung perfusion-assisted photodynamic therapy is then demonstrated, examining the maximally tolerated doses of 5-ALA and Chlorin e6 photosensitizers. Overall, the protocols and knowledge from this work will provide the basis for Phase 1 clinical trials assessing the safety of whole-lung perfusion assisted PDT.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".